PDF(Pubmed)
Abstract：
HIV-1 vaccines have been challenging to develop, partly due to the high level of genetic variation in its genome. Thus, a vaccine that can induce cross-reactive neutralization activities will be needed. Studies on the co-evolution of antibodies and viruses indicate that mimicking the natural infection is likely to induce broadly neutralizing antibodies (bnAbs). We generated the consensus Env sequence for each time point in subject CH505, who developed broad neutralization activities, and selected five critical time points before broad neutralization was detected. These consensus sequences were designed to express stable Env trimers. Priming with the transmitted/founder Env timer and sequential boosting with these consensus Env trimers from different time points induced broader and more potent neutralizing activities than the BG505 Env trimer in guinea pigs. Analysis of the neutralization profiles showed that sequential immunization of Env trimers favored nAbs with gp120/gp41 interface specificity while the BG505 Env trimer favored nAbs with V2 specificity. The unique features such as consensus sequences, stable Env trimers and the sequential immunization to mimic natural infection likely has allowed the induction of improved neutralization responses.
摘要：
HIV-1疫苗的开发一直面临挑战，部分原因是其基因组中高水平的遗传变异。因此，需要一种能诱导交叉反应中和活性的疫苗.对抗体和病毒共进化的研究表明,模拟自然感染可能诱导广泛中和抗体(bnAb)。我们在CH505受试者中产生了每个时间点的共有Env序列，他们产生了广泛的中和活性，并在检测到广泛中和之前选择五个关键时间点。设计这些共有序列以表达稳定的Env三聚体。与BG505Env三聚体相比，来自不同时间点的传输/创始人Env计时器的启动和用这些共识Env三聚体的顺序增强在豚鼠中诱导了更广泛和更有效的中和活性。中和谱的分析表明,Env三聚体的顺序免疫有利于具有gp120/gp41界面特异性的nAb,而BG505Env三聚体有利于具有V2特异性的nAb。独特的特征，如共有序列，稳定的Env三聚体和模拟自然感染的顺序免疫可能允许诱导改善的中和反应。
